Unexpected tandem reaction of new type moritabaylis- Hillman adducts promoted by [HMIM]HSO4/NANO3 system

Article abstract of DOI:10.3987/COM-11-12333

A tandem reaction of new type Baylis-Hillman adducts 1 was prompted by ionic liquid [Hmim]HSO₄/NaNO₃ system and the unexpected products 6-aryl-2H-pyran-3-carboxylates 2 and imidazolium salts 3 were efficiently formed via the rearrang

Full text of DOI:10.3987/COM-11-12333

HETEROCYCLES, Vol. 85, No. 1, 2012
43
HETEROCYCLES, Vol. 85, No. 1, 2012, pp. 43 - 56. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 9th August, 2011, Accepted, 8th November, 2011, Published online, 14th November, 2011
DOI: 10.3987/COM-11-12333
UNEXPECTED TANDEM REACTION OF NEW TYPE MORITA-
BAYLIS-HILLMAN ADDUCTS PROMOTED BY [HMIM]HSO4/NANO3
SYSTEM
Weihui Zhong,* Guan Wang, and Kai Chen
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College
of Pharmaceutical Sciences, Zhejiang University of Technology, Hangzhou
310014, P.R. China. Tel.&Fax:+86(571)88320867 E-mail: pharmlab@zjut.edu.cn
Abstract – A tandem reaction of new type Baylis-Hillman adducts 1 was
prompted by ionic liquid [Hmim]HSO4/NaNO3 system and the unexpected
products 6-aryl-2H-pyran-3-carboxylates 2 and imidazolium salts 3 were
efficiently formed via the rearrangement and substitution reaction. While
mediated by [Emim]HSO4/NaNO3 system, the key intermediates 4 were isolated.
A plausible mechanism for the transformation was given.
INTRODUCTION
Tandem reactions are of great importance in organic synthesis due to generation of some important
products in a single operation with high atom economy and bond-forming efficiency. Recently, more and
more novel types of tandem reactions, including tandem Michael addition,1 substitution,2 cyclization3-5
and rearrangement reaction,6 were extensively applied to organic synthesis, especially the synthesis of
natural optically active products7 and heterocyclic compounds. The Baylis-Hillman reaction is a
synthetically useful method for carbon-carbon bond-forming reactions to yield functionalized allylic
alcohols,8 thereby providing handles for further manipulation in a multitude of synthetic organic
transformations.9 In continuation of our research on new type Baylis-Hillman adducts 1 prepared from
aryl methyl ketones via a combination of the Vilsmeier and the Baylis-Hillman reactions,10-13 we
investigated the tandem reaction of new type Baylis-Hillman adduct 1 under the [Hmim]HSO4/NaNO3
system14 (Scheme 1). To our surprise, the unexpected products 6-aryl-2H-pyran-3-carboxylates 2 and/or
imidazolium salt 3 were isolated.

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HETEROCYCLES, Vol. 85, No. 1, 2012
Cl
OH
Cl
CO2R2
CO2R2
O
DABCO,
BTC / DMF
CHO
R1
R1
Vilsmeier
reaction
R1
Baylis-Hillman
reaction
new type BH adducts (1)
CO2R2
O
R1
Cl
2
CO2R2
CHO
anticipated products
[Hmim]HSO4
NaNO3, heat
[Hmim]HSO4
NaNO3, heat
Cl
R1
1
CO2R2
R1
N
N
HSO4
3
Scheme 1
RESULTS AND DISCUSSION
Initially, we mixed 1.0 mmol of (Z)-methyl 5-chloro-3-hydroxy-5-(4-methoxyphenyl)-2-methylenepent-
o
4-enoate 1a with 1.1 mmol of NaNO3 in ionic liquid [Hmim]HSO4 at 80 C for 12 h, the unexpected
product methyl 6-(4-methoxyphenyl)-2H-pyran-3-carboxylate 2a was isolated in 80% yield(Scheme 2).
CO2Me
Cl
OH
O
[Hmim]HSO4
CO2Me
NaNO3, 80 oC, 12 h
80%
MeO
MeO
1a
2a
Scheme 2
Encouraged by this result, several other nitrate salts have been used to investigate the above reaction and
the results were summarized in Table 1. No desired product 2a was detected using
NH4NO3-[Hmim]HSO4 system at 80 °C for 12 h (Table 1, entry 2). Zn(NO3)2-[Hmim]HSO4 system could
produce 2a with only 10% yield (Table 1, entry 3). Compared to the NaNO3-[Hmim]HSO4 system, a
slightly lower yield was found using KNO3-[Hmim]HSO4 system (Table 1, entry 4). The highest yield
(80%) of 2a was obtained in NaNO3-[Hmim]HSO4 system at 80 °C for 12 h (Table 1, entry 1). Moreover,
proper temperature was found to be essential to this reaction and the system showed homogeneous at
80 °C. At lower temperatures, 2a was obtained in lower yield even with longer reaction time (Table 1,
entries 5 and 6), while higher temperatures led to unknown side reactions and very complicated results
(Table 1, entries 7 and 8).

HETEROCYCLES, Vol. 85, No. 1, 2012
45
Table 1. Reaction of 1a with M(NO3)n-[Hmim]HSO4
CO2Me
Cl
OH
O
CO2Me
[Hmim]HSO4
M(NO3)n
MeO
MeO
2a
1a
Entry
M(NO3)n
NaNO3
NH4NO3
Zn(NO3)2
KNO3
Time (h)
Yielda of 2a (%)
Temp.( ℃)
1
2
3
4
5
6
7
8
80
12
12
12
12
72
48
10
10
80
0
80
80
10
78
0
80
NaNO3
NaNO3
NaNO3
NaNO3
40
60
34
67
46
100
120
a Isolated yield based on 1a.
Another type BH adduct 1b with a para-nitro group on the aromatic ring was also investigated under the
similar conditions. To our surprise, when substrate 1b was mixed with the NaNO3-[Hmim]HSO4 system
1
at 80 °C for 12h, only imidazolium salt 3b was isolated in 82%, which was confirmed by H-NMR,
13C-NMR and MS spectra (Scheme 3). This interesting result indicated that the different type of the
substituted groups on the aromatic ring had evident influence on the products.
Cl
Cl
OH
CO2Me
[Hmim]HSO4
CO2Me
NaNO3, 80 oC, 12 h O2N
82%
N
N
O2N
HSO4
1b
3b
Scheme 3
In order to confirm our presumption, various new type Baylis-Hillman adducts 1 were used for the
tandem rearrangement-substitution reaction under similar conditions and the full results are summarized
in Table 2. It was found that the substrates 1 with electron-donoring groups on the aromatic ring gave the
corresponding 2H-pyrans 2 in good yields (80-75%) (Table 2, entries 1, 3 and 4), while those with
electron-withdrawing groups produced the corresponding imidazolium salts 3 in good yields (98-78%)
(Table 2, entries 2, 6-9). Interestingly, the substrates 1e could give both of the products with the ratio of
2e : 3e = 1 : 2. In addition, when 2.2 equivalents of NaNO3 was added to this reaction, the ratio of these
two products was not obviously changed (Table 2, entry 5).

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HETEROCYCLES, Vol. 85, No. 1, 2012
Table 2. Reaction of new type BH adducts 1 with NaNO3-[Hmim]HSO4
Cl
CO2R2
Cl
OH
O
CO2R2
CO2R2
[Hmim]HSO4
NaNO3, 80 oC
R1
+
R1
R1
N
N
HSO4
1
2
3
Time
(h)
12
Yield of products a
Entry
Substrates
R1
R2
2
3
1
2
1a
1b
1c
1d
1e
1f
p-MeO
p-NO2
p-Me
p-MeO
H
Me
Me
Me
Et
2a (80)
-
-
12
3b (82)
-
3
13
2c (78)
2d (75)
2e (25)
-
4
5b
13
-
Me
Me
Et
12
3e (50)
3f (80)
3g (78)
3h (98)
3i (83)
6
m-Cl
p-NO2
p-F
11
7
1g
1h
1i
13
-
-
-
8
Me
Et
11
9
p-F
12
a Isolated yield based on 1.
b The ratio of 2e and 3e was not obviously changed when 2.2 mmol of NaNO3 was added.
In order to clarify the formation mechanism of these products, ionic liquid [Emim]HSO4 was prepared,15
which could avoid theoretical formation of imidazolium salts 3. As we anticipated, the reactions of the
Baylis-Hillman adducts 1 under the ionic liquid [Emim]HSO4/NaNO3 system gave SN2’ products
(2E,4Z)-5-chloro-2-(nitrooxymethyl)-5-arylpenta-2,4-dienoates 4 with satisfactory yields (Table 3).
Table 3. Reactions of new type BH adducts 1 with NaNO3-[Emim]HSO4
N
N
Cl
Cl
OH
HSO4
CO2R2
ONO2
CO2R2
R1
R1
NaNO3, rt.
1
4
Entry
Substrates
R1
R2
Me
Et
Time (h)
Yield of 4 a (%)
4a (65)
1
2
3
1a
1f
p-MeO
m-Cl
p-F
3
2
2
4b (76)
1h
Me
4c (83)
a Isolated yield based on 1.

HETEROCYCLES, Vol. 85, No. 1, 2012
47
However, these intermediates 4a-c were unstable at high temperature. Treatment of this intermediate 4a
with 3-methylbenzenethiol afforded the desired product (2Z,4Z)-methyl 5-chloro-5-(4-methoxyphenyl)-2-
(m-tolylthiomethyl)penta-2,4-dienoate 5a in 63% yield (Scheme 4).
Cl
Cl
[Emim]HSO4
CO2Me
CO2Me
m-MeC6H4SH
60 oC, 2 h
MeO
S
MeO
ONO2
63%
4a
5a
Scheme 4
To confirm the regularity, we used various of nucleophilic reagents to react with the Baylis-Hillman
adducts 1 under the ionic liquid [Emim]HSO4/NaNO3 system in one pot, and afforded the compounds
5a-i in good yields (Scheme 5, Table 4). During our experiments, we found without addition of NaNO3,
not desired compounds 5, but the rearrangemented compound 6 (R1= p-Cl) was isolated and conformed
by NMR and MS, which demonstrated the NaNO3 play an important role in the reactions, and the
intermediates 4 were existed in the reaction paths (Scheme 5). It was also found from Table 4 that the
substrates 1 with electron-donoring groups on the aromatic ring gave the higher yields than those with
electron-withdrawing groups. In other words, the more stable the intermediates 4 with electron-donoring
groups are, the more possible to form the 2H-pyrans 2 in [Hmim]HSO4/NaNO3 system.
Cl
Cl
OH
1. [Emim]HSO4
NaNO3, rt, 3 h
CO2Me
ONO2
CO2Me
R1
R1
1
4
[Emim]HSO4,
[Emim]HSO4,
nucleophilic
reagents
2. nucleophilic
reagents
nucleophilic
reagents
Cl
Cl
CO2Me
OH
CO2Me
Nu
R1
R1
6
5a-i
nucleophilic reagents: m-MeC6H4SH, p-MeC6H4SH, p-ClC6H4SH,
p-MeC6H4NH2, NaN3
Nu: m-MeC6H4S-, p-MeC6H4S-, p-ClC6H4S-, p-MeC6H4NH-, N3-
Scheme 5

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HETEROCYCLES, Vol. 85, No. 1, 2012
Table 4. Reactions of new type BH adducts 1 with NaNO3-[Emim]HSO4 and nucleophilic reagents
Entry Substrates
R1
Nu
Yield of 5 a (%)
5a (63)b
5b (83)
5c (81)
1
2
1a
1a
1a
1a
1a
1h
1h
1h
1h
p-MeO m-MeC6H4S
p-MeO p-MeC6H4S
3
p-MeO
p-ClC6H4S
4
5c
p-MeO p-MeC6H4NH
5d (78)
5e (76)
p-MeO
p-F
N3
6
p-MeC6H4S
p-ClC6H4S
p-MeC6H4NH
N3
5f (74)
7
p-F
5g (76)
8
9c
p-F
5h (67)
5i (70)
p-F
a Isolated yield based on 1.
b This reaction was carried out in two step and intermediate 4a was isolated.
c NaN3 was added dissolved in DMF.
According to the above results, a plausible mechanism16 for the formation of products 2, 3 and 4 was
shown in Scheme 6. Firstly, the BH adduct 1 was attacked by nitrate anion in ionic liquid to give SN2’
products 4, where [Hmim]HSO4 played a dual role of Brønsted acid catalyst and solvent for both
rearrangement and substitution.12 Intermediates 4 are unstable at high temperature and could be readily
converted into 2 and 3 via path A or path B dependent on the activities of substrates.
Cl
OH2
Cl
OH
CO2R2
NO3
O
-H2O
[Hmim]HSO4
NaNO3
CO2R2
R1
R1
1
CO2R2
Path A (R1 = EDG)
NO2 + Cl
Cl
CO2R2
R1
R1
2
O NO2
Cl
CO2R2
4
Path B (R1= EWG)
- NO3
[Hmim]HSO4
R1
N
N
HSO4
3
Scheme 6

HETEROCYCLES, Vol. 85, No. 1, 2012
49
In summary, the present study investigated the tandem reaction of new type Morita-Baylis-Hillman
adducts in ionic liquids/NaNO3 system, which provided a new and efficient way for the synthesis of
2H-pyrans and imidazolium salts. The new applications of ionic liquids/NaNO3 system are now being
investigated in our lab.
EXPERIMENTAL
Unless otherwise indicated, chemicals and solvents were purchased from commercial suppliers and
without further purification. Flash column chromatography was performed using silica gel (200-400
mesh). IR spectra were recorded on a Nicolet Avatar-370 instrument. Mass spectra were measured with
1
13
Termo Finnigan LCQ-Advantage. H NMR and C NMR spectra were recorded at VARAIN-400 or
BRUKER AVANCE III-500 using CDCl3 or DMSO as the solvent with tetramethylsilane (TMS) as an
internal standard at room temperature. Chemical shifts were given in  relative to TMS, the coupling
constants J were given in Hertz. The low-resolution mass spectra were obtained with the Thermo Trace
GC Ultra-DSQ II and Agilent 6120 (Quadrapole LC-MS) mass spectrometer. High resolution mass
spectra (HRMS) analyze were measured on an Agilent 6210 TOF LC/MS using ESI or EI (electrospray
ionization) techniques.
General procedure for the synthesis of 2H-pyrans 2 and/or imidazolium salts 3
A mixture of Baylis-Hillman adducts 1 (1 mmol) and NaNO3 (1.1 mmol) was stirred in 2 mL of
[Hmim]HSO4 at 80 °C for 12 h. The reaction mixture was cooled to rt. After completion of the reaction
(monitored by TLC), the product was extracted with EtOAc (3 × 10 mL). The combined extract was dried
over Na2SO4, filtered, concentrated under reduced pressure, and purified by silica gel column
chromatography (CH2Cl2-MeOH, 16 :1 ) to afford the products 2 and 3.
General procedure for the synthesis of (2E,4Z)-5-chloro-2-(nitrooxymethyl)-5-arylpenta-2,4-
dienoates 4
A mixture of Baylis-Hillman adducts 1 (1 mmol) and NaNO3 (1.1 mmol) was stirred in 2 mL of
[Emim]HSO4 at rt for 3 h. After completion of the reaction (monitored by TLC), the product was
extracted with EtOAc (3 × 10 mL). The combined extract was dried over Na2SO4, filtered, concentrated
under reduced pressure, and purified by silica gel column chromatography (hexane-EtOAc, 8:1) to afford
the desired products 4.
General procedure for the synthesis of compounds 5
A mixture of Baylis-Hillman adducts 1 (1 mmol) and NaNO3 (1.1 mmol) was stirred in 2 mL of

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HETEROCYCLES, Vol. 85, No. 1, 2012
[Emim]HSO4 at rt for 3 h. The reaction mixture was heat to 60 °C and o-MeC6H4SH (1.1 mmol) was
added. The mixture was further stirred at rt for 2-3 h. After completion of the reaction (monitored by
TLC), the product was extracted with EtOAc (3 × 10 mL). The combined extract was dried over Na2SO4,
filtered, concentrated under reduced pressure, and purified by silica gel column chromatography
(hexane-EtOAc, 8:1) to afford the desired product 5.
Methyl 6-(4-methoxyphenyl)-2H-pyran-3-carboxylate (2a)
1
White solid. Mp 166-169 °C. IR (KBr) (νmax, cm-1): 3188, 2936, 1670. H NMR (400 MHz, DMSO-d6)
δH: 3.75 (3H, s, COOCH3), 3.82 (3H, s, Ar-OCH3), 4.66 (2H, s, O-CH2-C=C), 7.04-7.79 (4H, m, ArH),
7.61 (1H, d, J = 11.2 Hz, O-C=CH-C), 7.73 (1H, d, J = 11.2 Hz, CH=C-COOMe). 13C NMR (100 MHz,
DMSO-d6) δC: 52.1, 55.5, 59.8, 92.2, 104.5, 114.3(2C), 119.1, 128.4, 128.7, 137.5, 139.8, 161.0, 166.6;
MS (CI) 246.0 [M]+. HRMS (CI) calcd for [C14H14O4]: 246.0892; found: 246.0895.
Methyl 6-p-tolyl-2H-pyran-3-carboxylate (2c)
1
White solid. Mp 166-169 °C. IR (KBr) (νmax, cm-1): 3183, 2943, 1674. H-NMR (400 MHz, DMSO-d6)
δH: 2.36 (3H, s, Ar-CH3), 3.76 (3H, s, COOCH3), 4.67 (2H, s, OCH2C), 7.30 (1H, d, J = 8.0, O-C=CH),
7.64-7.71 (4H, m, ArH), 7.74 (1H, d, J = 2.8, MeOOC-C=CH); 13C NMR (100 MHz, DMSO-d6) δC: 20.8,
52.1, 59.8, 120.2, 126.6(2C), 129.4(2C), 129.5, 133.2, 137.1, 139.9, 140.4, 166.6; MS (CI) 231.3 [M+1]+.
HRMS (CI) calcd for [C14H14O3]: 230.0943; found: 230.0939.
Ethyl 6-(4-methoxyphenyl)-2H-pyran-3-carboxylate (2d)
1
White solid. Mp 166-169 °C. IR (KBr) (νmax, cm-1): 3176, 2945, 1665. H NMR (400 MHz, DMSO-d6)
δH: 1.27 (3H, t, J = 7.2, CH2CH3), 3.82 (3H, s, Ar-OCH3), 4.42 (2H, q, J = 7.2, CH2CH3), 4.66 (2H, s,
OCH2), 7.04 (2H, m, ArH), 7.62 (1H, d, J = 11.2, C=CH-CH=C-O), 7.73 (1H, d, J = 11.2, C=CH-
CH=C-O), 7.78-7.80 (2H, m, ArH); 13C NMR (100 MHz, DMSO-d6) δC: 14.1, 55.4, 59.8, 60.6, 144.2(2C),
119.1, 128.3(2C), 128.9, 137.2, 139.5, 160.9, 166.1(2C); MS (CI) 261.3 [M+1]+. HRMS (CI) calcd for
[C15H16O4]: 260.1049; found: 260.1045.
Methyl 6-phenyl-2H-pyran-3-carboxylate (2e)
1
White solid. Mp 163-165 °C. IR (KBr) (νmax, cm-1): 3163, 2959, 1660. H NMR (400 MHz, DMSO-d6)
δH: 3.87 (3H, s, COOCH3), 4.42 (2H, s, OCH2C), 7.30 (1H, d, J = 11.2, O-C=CH), 7.24 (H, s, ArH), 7.42
(2H, d, J = 3.6, ArH), 7.73 (2H, d, J = 3.6, ArH), 7.42 (2H, d, J = 11.2, MeOOC-C=CH); 13C NMR (100
MHz, DMSO-d6) δC: 52.1, 59.8, 121.0, 126.6(2C), 128.8(2C), 129.9, 130.3, 135.9, 136.9, 139.7, 166.5;
MS (ESI) 217.1 [M+1]+. HRMS (ESI) calcd for [C13H12O3]: 216.0786; found: 216.0780.

HETEROCYCLES, Vol. 85, No. 1, 2012
51
1-((2E,4Z)-5-Chloro-2-(methoxycarbonyl)-5-(4-nitrophenyl)penta-2,4-dienyl)-3-methyl-1H-imidazol-
3-iumhydrogensulfate (3b)
Yellow solid. Mp 260-262 °C. IR (KBr) (νmax, cm-1): 3442, 2945, 1694. 1H NMR (400 MHz, DMSO-d6)
δH: δ (ppm) 3.77 (3H, s, N-CH3), 3.86 (3H, s, COOCH3), 5.43 (2H, s, N-CH2), 7.36-7.40 (2H, m, ArH),
7.77 (1H, d, J = 5.6 Hz, Cl-C=CH), 7.86 (1H, d, J = 11.2 Hz, Me-N-CH=C), 7.95 (1H, d, J = 11.2 Hz,
13
N-CH=C), 8.06 (1H, d, J = 5.6 Hz, ClC=C-CH=C), 8.07-8.09 (2H, m, ArH), 9.21 (1H, s, N=CH-C). C
NMR (100 MHz, DMSO-d6) δC: 36.8, 52.1, 59.8, 121.0, 126.7(2C), 128.8(2C), 129.9, 130.3, 135.9, 136.9,
+
139.6, 141.8, 147.4, 148.0, 166.5; MS (ESI) 362.1 [M]+. HRMS (ESI) calcd for [C17H17ClN3O4 ]:
362.0908; found: 362.0900.
3-((2E,4Z)-5-Chloro-2-(methoxycarbonyl)-5-phenylpenta-2,4-dienyl)-1-methyl-1H-imidazol-3-ium-
hydrogensulfate (3e)
1
White solid. Mp 260-262 °C. IR (KBr) (νmax, cm-1): 3443, 2942, 1699. H NMR (400 MHz, DMSO-d6)
δH: 3.76 (3H, s, N-CH3), 3.86 (3H, s, COOCH3), 4.67 (2H, s, N-CH2), 7.29 (2H, d, J = 8.8 Hz, ArH), 7.65
(2H, d, J = 3.2 Hz, Cl-C=CH, ClC=C-CH=C), 7.66 (2H, d, J = 6.4 Hz, Me-N-CH=C, N-CH=C), 7.70 (2H,
d, J = 8.8 Hz, ArH), 7.74 (H, d, J = 3.2 Hz, ArH), 9.03 (1H, s, N=CH-C). 13C NMR (100 MHz,
DMSO-d6) δC: 35.8, 44.8, 61.2, 118.7, 122.7, 123.5, 125.7, 127.3(2C), 129.3(2C), 133.0, 136.7, 139.1,
+
141.0, 143.1, 165.4; MS (ESI) 317.1 [M]+. HRMS (ESI) calcd for [C17H18ClN2O2 ]: 317.1057; found:
317.1062.
3-((2E,4Z)-5-Chloro-5-(3-chlorophenyl)-2-(methoxycarbonyl)penta-2,4-dienyl)-1-methyl-1H-imid-a
zol-3-ium hydrogensulfate (3f)
1
White solid. Mp 265-268 °C. IR (KBr) (νmax, cm-1): 3456, 2938, 1676. H NMR (400 MHz, DMSO-d6)
δH: 3.77 (3H, s, N-CH3), 3.87 (3H, s, COOCH3), 5.44 (2H, s, N-CH2), 7.54-7.58 (2H, m, ArH), 7.59-7.61
(2H, m, ArH), 7.73 (1H, d, J = 13.6 Hz, Me-N-CH=C), 7.75 (1H, d, J = 8.8 Hz, Cl-C=CH), 7.94 (1H, d, J
= 13.6 Hz, N-CH=C), 7.95 (1H, d, J = 8.8 Hz, ClC=C-CH=C), 9.20 (1H, s, N=CH-C). 13C NMR (100
MHz, DMSO-d6) δC: 35.9, 44.7, 52.6, 121.1, 122.7, 123.5, 126.2, 126.7, 126.9, 130.5, 130.7, 133.7, 136.8,
+
137.7, 138.6, 140.8, 165.8; MS (ESI) 351.0 [M]+. HRMS (ESI) calcd for [C17H17Cl2N2O2 ]: 351.0667;
found: 351.0653.
3-((2E,4Z)-5-Chloro-2-(ethoxycarbonyl)-5-(4-nitrophenyl)penta-2,4-dienyl)-1-methyl-1H-imidazol-
3-ium hydrogensulfate (3g)
Yellow solid. Mp 272-273 °C. IR (KBr) (νmax, cm-1): 3469, 2934, 1689. 1H NMR (400 MHz, DMSO-d6)
δH: 1.24 (3H, t, J = 7.2, COOCH2CH3), 3.86 (3H, s, N-CH3), 4.22 (2H, q, J = 7.2, COOCH2CH3), 5.48
(2H, s, N-CH2), 7.73-7.78 (2H, m, N-HC=CH-N), 7.95 (1H, d, J = 11,6, ClC=C-CH=C), 8.12 (1H, d, J =
13
11.2, ClC=HC-C=C), 8.29-8.34 (4H, m, ArH), 9.24 (1H, s, N=CH-N); C NMR (100 MHz, DMSO-d6)

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HETEROCYCLES, Vol. 85, No. 1, 2012
δC: 13.9, 35.8, 44.8, 61.5, 122.8, 123.5, 123.8(2C), 128.3, 128.7(2C), 136.9, 138.1, 139.9, 141.5,
+
148.2(2C), 165.1; MS (ESI) 376.1 [M]+. HRMS (ESI) calcd for [C18H19ClN3O4 ]: 376.1064; found:
376.1067.
1-((2E,4Z)-5-Chloro-5-(4-fluorophenyl)-2-(methoxycarbonyl)penta-2,4-dienyl)-3-methyl-1H-imid-
azol-3-ium hydrogensulfate (3h)
1
White solid. Mp 257-258 °C. IR (KBr) (νmax, cm-1): 3455, 2940, 1705. H NMR (400 MHz, DMSO-d6)
δH: 3.77 (3H, s, N-CH3), 3.86 (3H, s, COOCH3), 5.43 (2H, s, N-CH2), 7.38 (2H, t, J = 8.8 Hz, ArH), 7.23
(1H, d, J = 3.6 Hz, Cl-C=CH), 7.64 (1H, d, J = 3.6 Hz, ClC=C-CH=C), 7.86 (1H, d, J = 11.2 Hz,
Me-N-CH=C), 7.95 (1H, d, J = 11.2 Hz, N-CH=C), 8.06-8.09 (2H, m, ArH), 9.21 (1H, s, N=CH-C). 13C
NMR (100 MHz, DMSO-d6) δC: 35.8, 44.8, 52.6, 115.8 (J = 22 Hz, 2C), 119.7, 122.6, 123.5, 126.1, 130.0
(J = 9 Hz, 2C), 132.3, 136.8, 139.0, 141.7, 162.2, 165.9; MS (ESI) 335.0 [M]+. HRMS (ESI) calcd for
+
[C17H17ClFN2O2 ]: 335.0963; found: 335.0962.
3-((2E,4Z)-5-Chloro-2-(ethoxycarbonyl)-5-(4-fluorophenyl)penta-2,4-dienyl)-1-methyl-1H-imidazol-
3-ium hydrogensulfate (3i)
1
White solid. Mp 263-266 °C. IR (KBr) (νmax, cm-1): 3449, 2966, 1673. H NMR (400 MHz, DMSO-d6)
δH: 1.24 (3H, t, J = 7.2, COOCH2CH3), 3.72 (3H, s, N-CH3), 4.20 (2H, q, J = 7.2Hz, COOCH2CH3), 5.37
(2H, s, N-CH2), 7.39 (2H, t, J = 8.8 Hz, ArH), 7.68 (1H, t, J = 1.6Hz N-HC=CH-N), 7.72 (1H, t, J = 1.6
Hz, N-HC=CH-N), 7.77 (1H, d, J = 11.6, ClC=HC-C=C), 7.95 (1H, d, J = 11.6 Hz, ClC=C-CH=C), 8.02
13
(2H, m, J1 = 5.6 Hz, J2=9.2Hz, ArH), 9.10 (1H, s, N=CH-N); C NMR (100 MHz, DMSO-d6) δC: 14.1,
36.0, 44.9, 61.5, 115.9 (J = 22 Hz, 2C), 119.7, 122.8, 123.6, 126.3, 130.0 (J = 9 Hz, 2C), 132.5, 136.8,
+
138.9, 141.8, 163.7 (J = 226 Hz), 165.5; MS (ESI) 349.1 [M]+. HRMS (ESI) calcd for [C18H19ClFN2O2 ]:
349.1119; found: 349.1102.
(2E,4Z)-Methyl-5-chloro-5-(4-methoxyphenyl)-2-(nitrooxymethyl)penta-2,4-dienoate(4a)
1
Yellow solid. Mp 78-80 °C. IR (KBr) (νmax, cm-1): 3157, 2925, 1656. H-NMR (CDCl3, 400 MHz): δ
(ppm) 3.84 (3H, s, CH3), 3.85 (3H, s, CH3), 4.42 (2H, s, CH2), 6.91-6.93 (2H, m, ArH), 6.99 (1H, d, J =
13
11.6 Hz, CH=CH), 7.67-7.70 (2H, m, ArH), 7.87 (1H, d, J = 11.6 Hz, CH=CH). C-NMR (100 MHz,
CDCl3) δ (ppm) 25.3, 52.8, 55.8, 114.3(2C), 118.0, 128.6, 128.8(2C), 129.6, 137.9, 143.2, 161.5, 166.3.
MS (EI): m/z (%) = 265(69, M-62), 223(71), 205(92), 179(100). HRMS (EI) calcd for [C14H14ClNO6]:
327.0510; found: 327.0515.
(2E,4Z)-Ethyl-5-chloro-5-(3-chlorophenyl)-2-(nitrooxymethyl)penta-2,4-dienoate(4b)
1
White solid. Mp 80-83 °C. IR (KBr) (νmax, cm-1): 3139, 2921, 1671. H-NMR (CDCl3, 400 MHz): δ

HETEROCYCLES, Vol. 85, No. 1, 2012
53
(ppm) 1.37 (3H, t, J = 7.2 Hz, CH2CH3), 4.32 (2H, q, J1 = 7.2 Hz, J2 = 14.4 Hz, CH2CH3), 4.41 (2H, s,
CH2), 7.06 (1H, d, J = 11.2 Hz, CH=CH), 7.33-7.38 (2H, m, ArH), 7.58-7.69 (2H, m, ArH), 7.82 (1H, d, J
13
= 11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ (ppm) 29.7, 37.4, 52.5, 119.8, 123.7, 128.3, 128.9,
129.7, 130.7, 135.3, 136.5, 137.4, 141.9, 166.2. MS (EI): m/z (%) = 329 (5, [M-16]+), 283(32), 237(100).
HRMS (EI) calcd for [C14H13Cl2NO5]: 345.0171; found: 345.0175.
(2E,4Z)-Methyl-5-chloro-5-(4-fluorophenyl)-2-(nitrooxymethyl)penta-2,4-dienoate(4c)
1
White solid. Mp 85-87 °C. IR (KBr) (νmax, cm-1): 3148, 2959, 1668. H-NMR (CDCl3, 400 MHz): δ
(ppm) 3.86 (3H, s, CH3), 4.40 (2H, s, CH2), 7.01 (1H, d, J = 11.2 Hz, CH=CH), 7.13-7.08 (2H, m, ArH),
7.82-7.70 (2H, m, ArH), 7.84 (1H, d, J = 11.6 Hz, CH=CH). 13C-NMR (100 MHz, CDCl3) δ (ppm) 24.5,
52.5, 115.7 (J = 22 Hz, 2C), 119.4, 128.9 (J = 8 Hz, 2C), 129.6, 133.1, 136.9, 141.6, 163.6 (J = 250 Hz),
165.8. MS (EI): m/z (%) = 299 (12, [M-16]+), 253(37), 221(100), 193(77), 157(32). HRMS (EI) calcd for
[C13H11ClFNO5]: 315.0310; found: 315.0308.
(2Z,4Z)-Methyl-5-chloro-5-(4-methoxyphenyl)-2-(m-tolylthiomethyl)penta-2,4-dienoate (5a)
Yellow liquid. IR (KBr) (νmax, cm-1): 3134, 2955, 1661. 1H-NMR (CDCl3, 400MHz): δ (ppm) 2.24 (3H, s,
CH3), 3.82 (3H, s, CO2CH3), 3.83 (3H, s, OCH3), 3.91 (2H, s, SCH2), 6.44 (1H, d, J = 12 Hz, CH=CH),
6.84 (2H, dd, J1 = 2 Hz, J2 = 4.4 Hz, ArH), 6.95 (1H, d, J = 4.0 Hz, ArH), 7.13-7.09 (1H, m, ArH),
7.27-7.24 (2H, m, ArH), 7.41-7.39 (2H, dd, J1 = 2 Hz, J2 = 3.2 Hz, ArH), 7.73 (1H, d, J = 11.6 Hz,
13
CH=CH). C-NMR (CDCl3, 100MHz): δ (ppm) 21.3, 32.8, 52.3, 55.5, 113.6(2C), 118.3, 128.2(2C),
128.4, 128.6, 129.5, 129.9, 130.8, 133.3, 134.9, 135.5, 138.6, 140.4, 160.7, 167.1; MS (EI): m/z (%) =
388 (5, M+), 265(100), 233(80), 205(55), 179(52). HRMS (EI) calcd for [C21H21ClO3S]: 388.0900; found:
388.0904.
(2Z,4Z)-Methyl 5-chloro-5-(4-methoxyphenyl)-2-(p-tolylthiomethyl)penta-2,4-dienoate (5b)
Yellow liquid. IR (KBr) (νmax, cm-1): 3135, 2942, 1689. 1H-NMR (CDCl3, 400 MHz)：δ (ppm) 2.24 (3H, s,
CH3), 3.67 (3H, s, CH3), 3.82 (3H, s, CH3), 3.91 (2H, s, CH2), 6.40 (1H, d, J = 11.2 Hz, CH=CH), 6.58
(2H, d, J = 8.8 Hz, ArH), 6.73-6.86 (4H, m, ArH), 7.38 (2H, d, J = 8.8 Hz, ArH), 7.73 (1H, d, J = 11.2 Hz,
CH=CH). 13C-NMR (100 MHz, CDCl3) δ (ppm) 21.2, 39.1, 52.2, 56.0, 114.8(2C), 126.6, 126.9,
128.8(2C), 129.3(2C), 130.1(2C), 131.8, 132.9, 136.7, 136.8, 136.9, 161.5, 163.4. MS (ESI) 389.9
[M+1]+. HRMS (ESI) calcd for [C21H21ClO3S]: 388.9076; found: 388.9082.
(2Z,4Z)-Methyl-5-chloro-2-((4-chlorophenylthio)methyl)-5-(4-methoxyphenyl)penta-2,4-dienoate
(5c)
Yellow liquid. IR (KBr) (νmax, cm-1): 3157, 2925, 1656. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 3.87 (3H, s,

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HETEROCYCLES, Vol. 85, No. 1, 2012
CH3), 3.90 (3H, s, CH3), 3.95(2H, s, CH2), 6.94 (1H, d, J = 11.2 Hz, CH=CH), 7.26-7.54 (8H, m, ArH),
13
7.7 7(1H, d, J =11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ (ppm) 39.1, 52.1, 56.0, 114.8(2C),
126.5, 126.9, 128.9(2C), 129.3(2C), 131.6(2C), 131.8, 133.1, 134.3, 136.7, 136.9, 161.5, 163.4. MS (ESI)
410.2 [M+1]+. HRMS (ESI) calcd for [C20H18Cl2O3S]: 409.3261; found: 409.3269.
(2E,4Z)-Methyl-5-chloro-5-(4-methoxyphenyl)-2-((p-tolylamino)methyl)penta-2,4-dienoate (5d)
Yellow liquid. IR (KBr) (νmax, cm-1): 3457, 3130, 2931, 1650. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 2.21
(3H, s, CH3), 3.60 (3H, s, CH3), 3.84 (3H, s, CH3), 4.14 (2H, s, CH2), 6.48 (1H, d, J = 11.2 Hz, CH=CH),
6.65 (2H, d, J = 8.8 Hz, ArH), 6.73-6.80 (4H, m, ArH), 7.28 (2H, d, J = 8.8 Hz, ArH), 7.74 (1H, d, J =
13
11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ (ppm) 21.1, 41.8, 52.0, 56.0, 114.3(2C), 114.8(2C),
126.5, 126.7, 128.9(2C), 130.0(2C), 131.8, 135.1, 136.7, 140.7, 144.9, 161.5, 166.7. MS (ESI) 372.9
[M+1]+. HRMS (ESI) calcd for [C21H22ClNO3]: 371.8573; found: 371.8564.
(2E,4Z)-Methyl-2-(azidomethyl)-5-chloro-5-(4-methoxyphenyl)penta-2,4-dienoate (5e)
Yellow liquid. IR (KBr) (νmax, cm-1): 3154, 2922, 1956, 1658. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 3.81
(3H, s, CH3), 3.83 (3H, s, CH3), 4.23 (2H, s, CH2), 6.91-6.93 (2H, m, ArH), 7.01 (1H, d, J = 11.2 Hz,
13
CH=CH), 7.77-7.80 (2H, m, ArH), 7.88 (1H, d, J =11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ
(ppm) 49.4, 52.0, 56.0, 114.8(2C), 126.5, 128.9(2C), 131.8, 135.8, 136.7, 138.1, 161.5, 167.2. MS (ESI)
308.7 [M+1]+. HRMS (ESI) calcd for [C14H14ClN3O3]: 307.7323; found: 307.7326.
(2Z,4Z)-Methyl-5-chloro-5-(4-fluorophenyl)-2-(p-tolylthiomethyl)penta-2,4-dienoate (5f)
Yellow liquid. IR (KBr) (νmax, cm-1): 3149, 2933, 1641. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 2.47 (3H, s,
CH3), 3.82 (3H, s, CH3), 3.91 (2H, s, CH2), 7.01 (1H, d, J = 11.2 Hz, CH=CH), 7.35-7.37 (4H, m, ArH),
7.49-7.83 (4H, m, ArH), 7.84 (1H, d, J = 11.2 Hz, CH=CH). 13C-NMR (100 MHz, CDCl3) δ (ppm) 21.3,
32.1, 52.3, 115.4(2C), 119.8, 128.0(2C), 129.2(2C), 131.6, 131.7(2C), 133.1 (J = 61 Hz), 137.5, 140.3,
146.4, 147.9 (J = 37 Hz), 162.1, 167.2. MS (ESI) 377.9 [M+1]+. HRMS (ESI) calcd for [C20H18ClFO2S]:
376.8721; found: 376.8719.
(2Z,4Z)-Methyl-5-chloro-2-((4-chlorophenylthio)methyl)-5-(4-fluorophenyl)penta-2,4-dienoate (5g)
Yellow liquid. IR (KBr) (νmax, cm-1): 3174, 2934, 1689. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 3.88 (3H, s,
CH3), 3.94 (2H, s, CH2), 7.00 (1H, d, J = 11.2 Hz, CH=CH), 7.21-7.31 (4H, m, ArH), 7.47-7.63 (4H, m,
13
ArH), 7.84 (1H, d, J = 11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ (ppm) 32.1, 52.3, 115.4(2C),
119.8, 128.0(2C), 129.0(2C), 130.7, 131.2(2C), 132.2 (J = 123 Hz), 134.5, 140.3, 146.3, 147.9 (J = 32
Hz), 162.1, 167.2. MS (ESI) 398.3 [M+1]+. HRMS (ESI) calcd for [C19H15Cl2FO2S]: 397.2906; found:
397.2914.

HETEROCYCLES, Vol. 85, No. 1, 2012
55
(2E,4Z)-Methyl-5-chloro-5-(4-fluorophenyl)-2-[(p-tolylamino)methyl]penta-2,4-dienoate (5h)
1
Yellow liquid. IR (KBr) (νmax, cm-1): 3467, 3199, 2913, 1687. H-NMR (CDCl3, 400 MHz): δ (ppm)
2.43 (3H, s, CH3), 3.85 (3H, s, CH3), 4.12 (2H, s, CH2), 7.01 (1H, d, J = 11.2 Hz, CH=CH), 7.31-7.37
(4H, m, ArH), 7.64-7.74 (4H, m, ArH), 7.84 (1H, d, J = 11.2 Hz, CH=CH). 13C-NMR (100 MHz, CDCl3)
δ (ppm) 21.3, 48.5, 52.3, 113.4 (2C), 115.4 (2C), 119.8, 128.0 (2C), 129.6, 130.7 (J = 180 Hz, 2C), 134.4,
139.3, 144.6, 146.2, 147.9 (J = 30 Hz), 162.1, 167.1. MS (ESI) 360.8 [M+1]+. HRMS (ESI) calcd for
[C20H19ClFNO2]: 359.8218; found: 359.8215.
(2E,4Z)-Methyl-2-(azidomethyl)-5-chloro-5-(4-fluorophenyl)penta-2,4-dienoate (5i)
Yellow liquid. IR (KBr) (νmax, cm-1): 3145, 2911, 1949, 1662. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 3.84
(3H, s, CH3), 4.22 (2H, s, CH2), 7.01 (1H, d, J = 11.2 Hz, CH=CH), 7.13-7.18 (2H, m, ArH), 7.67-7.69
13
(2H, m, ArH), 7.87 (1H, d, J = 11.2 Hz, CH=CH). C-NMR (100 MHz, CDCl3) δ (ppm) 49.4, 52.0,
115.0 (2C), 126.5, 130.9 (J = 132 Hz, 2C), 134.0, 136.3 (J = 89 Hz), 138.1, 141.6, 162.9 (J = 101 Hz),
167.2. MS (ESI) 296.7 [M+1]+. HRMS (EI) calcd for [C13H11ClFN3O2]: 295.6967; found: 295.6959.
(2E,4Z)-Methyl-5-chloro-5-(4-chlorophenyl)-2-(hydroxymethyl)penta-2,4-dienoate (6)
Yellow liquid. IR (KBr) (νmax, cm-1): 3644, 2953, 1648. 1H-NMR (CDCl3, 400 MHz): δ (ppm) 3.87 (3H, s,
CH3), 4.51 (2H, s, CH2), 7.09 (1H, d, J = 11.2 Hz, CH=CH), 7.09-7.41 (2H, m, ArH), 7.65-7.68 (2H, m,
ArH), 7.89 (1H, d, J = 11.2 Hz, CH=CH). 13C-NMR (100 MHz, CDCl3) δ (ppm) 37.4, 52.5, 119.8, 123.7,
128.3 (2C), 128.9 (2C), 129.7, 130.7, 135.4, 136.5, 166.2. MS (ESI) 288.4 [M+1]+. HRMS (ESI) calcd
for [C13H12Cl2O3]: 287.1386; found: 287.1380.
ACKNOWLEDGEMENTS
We thank the National Natural Science Foundation of China [21076194] for financial support.
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